ASH: Celebrex Easier Than Nonselective NSAIDs on Blood Pressure

Action Points

Be aware that this report suggests that Celebrex (celecoxib) is associated with less blood pressure destabilization and edema than nonselective NSAIDs.

This study was published as an abstract and presented in a poster at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

NEW YORK, May 19 â€” Celebrex (celecoxib), the Cox-2 inhibitor, increases blood pressure compared with placebo, but the rise is not as great as it is among patients taking Advil (ibuprofen), Aleve (naproxen), or other nonselective NSAIDs.

"Numerically, [Celebrex] is somewhere in the middle between placebo, which doesn't raise blood pressure at all, and nonselective NSAIDs, which raise blood pressure significantly more than the Cox-2 inhibitor," William B. White, M.D. of the University of Connecticut School of Medicine in Farmington reported at the American Society of Hypertension meeting here.

That finding emerged from a meta-analysis of data from 44,308 patients enrolled in 41 studies that are included in a Celebrex database for chronic diseases (osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain and Alzheimer's disease).

Moreover, compared with patients taking NSAIDs patients receiving Celebrex were significantly less likely to develop edema (P=0.001) and also had a lower rate of cardiac failure, although the difference was not statistically significant (P=0.056), he said.

Both NSAIDs and Cox-2 inhibitors have an antinatriuretic effect, decreasing water and sodium excretion, leading to an increase in blood pressure and the development of edema. In addition, NSAIDs appear to inhibit the production of vasodilatory prostaglandins.

"We're not 100% certain about the mechanisms of the differences in blood pressure destabilization with [Celebrex] compared with the other NSAIDs," Dr. White said in an interview. "But a couple of things that come to mind is that [Celebrex] has a relatively short half life, which allows the kidney to recuperate somewhat between doses and excrete some salt and water."

A second possibility, he said, is that Celebrex has a unique molecular structure that gives it a weak diuretic effect through carbonic anhydrase inhibition that allow excretion of both bicarbonate and water that may well overcome the anti-prostacyclin effect of the drug.

Interest in cardiovascular safety of Cox-2 inhibitors has been high since Vioxx (rofecoxib) was voluntarily removed from the market in September 2004. Merck reported that the drug was associated with an increased risk of non-fatal heart attacks among those participating in a colon cancer prevention study who took the drug daily for more than 18 months.

Since that time hundreds of lawsuits have been filed against Merck, and other studies have reported increased cardiovascular events associated with a number of NSAIDs. In April 2005 the FDA issued new guidelines for the use of all NSAIDsâ€”except aspirinâ€”and Pfizer voluntarily pulled Bextra (valdecoxib), another Cox-2 inhibitor, from the market. Celebrex, also made by Pfizer, is the only Cox-2 inhibitor still on the market.

The controversy surrounding the use of Celebrex and other NSAIDs caused American Society of Hypertension to remove Dr. White's paper from the agenda of a press briefing. The paper was featured in press materials distributed several weeks ago, but Dr. White said he was later informed that the issue was "too controversial" so he was "told not to come to the press room."

In response to Dr. White's comment, ASH released this statement: "As an organization, ASH didn't want to take sides on the various issues surrounding the Cex-2 inhibitors by highlighting any one piece of data."

In the meta-analysis, 24,933 patients received Celebrex at doses ranging from 50 to 800 mg a day, 13,990 received naproxen, diclofenac, ibuprofen, ketoprofen, or loxoprofen, and 4,057 received placebo.

The studies were well balanced and about two-thirds of the participants were women. The overwhelming majority of studies were in patients with osteoarthritis and the treatment duration was often short-just two weeks in some studies. "But it is important to point out that we included data from an Alzheimer's disease trial in which patients took high-dose [Celebrex] for two years," Dr. White said. "That trial had the highest event rate."

Two percent of patients taking Celebrex developed edema versus 0.9% of placebo patients (P<0.001), 1.1% of Celebrex patients developed hypertension or aggravated hypertension versus 0.7% of placebo patients (P=0.023), and 0.2% of Celebrex patients had cardiac failure versus less than 0.1% of placebo patients (P=0.046).

By contrast when Celebrex was compared with NSAIDs 1.5% of Celebrex-treated patients developed hypertension versus 2% of NSAID patients (P=0.002) and 2.4% of the Celebrex patients developed edema versus 3% in the NSAID group (P=0.001).

Dr. White said that the even though the analysis represents a relatively high number of accumulated patient-years of treatment exposure, "exposure duration in any individual may not have been sufficient to permit development of adverse outcomes."

Dr. White and his colleagues from Harvard Medical School, the University of Dundee In Scotland, and Weill Medical College of Cornell in New York, worked with data from Pfizer. But the study "was purely an academic endeavor," he said. "We received no funding from Pfizer and we didn't apply for any grants to conduct this study."

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.